POS0238 SIDE EFFECT PROFILE OF HYDROXYCHLOROQUINE USE IN PATIENTS WITH RA, SLE, AND OTHER RMDs OVER 20 YEARS
Authors: K. Michaud, S. Pedro
Journal: Annals of the Rheumatic Diseases (2022)

Background During the pandemic, hydroxychloroquine (HCQ) became a household name, yet despite more than 70 years as a csDMARD treatment, relatively little is known about its overall side effect (SE) profile. Objectives To understand the types, severity, and rates of patient-reported side effects of HCQ in adults with RA, SLE, and other RMDs alone and in comparison with methotrexate (MTX). Methods Adult participants in the Forward Databank observational registry reported all medication use and medication side effects through biannual questionnaires from 1999 through 2021. Incident use of HCQ and MTX were measured at enrollment and longitudinally with additional reporting of severity of side effects, certainty of medication as cause of side effect, and affected body systems. We analyzed incident rates of side effects overall and by HCQ or MTX categorical use, respectively: monotherapy, with concomitant use of another csDMARD, or with concomitant use of a bDMARD or tsDMARD. Finally, the likelihood of having any side effects was analyzed in Cox regression models by comparing HCQ initiators to MTX initiation, and within each, combination MTX or HCQ with csDMARD or bDMARD to monotherapy; these models were adjusted for age, sex, RD Comorbidity Index, patient global, pain, disease duration, and number of bDMARDs used. Results Overall, 5874 patients initiated HCQ and 10420 initiated MTX, with RA as the predominant diagnosis. Mean baseline characteristics were similar for RA: 59 years old, 80% female and 12 years of RA duration. HCQ was mostly used with other csDMARDs, while MTX was mostly used with bDMARDs. In the other RMD and SLE groups, most were on HCQ monotherapy. For all RMDs, SE incidence for HCQ (16 – 17%) was lower than MTX (26 – 39%). The Table 1 provides incidence rates by HCQ/MTX for any SE, a SE that forces medication discontinuation, and SE leading to hospitalization. Reported SE rates were always higher for MTX vs. HCQ for all SE severity and diagnoses. Table 1. Incidence rates (IR) per 1000 patient-years of SEs by diagnoses for HCQ and MTX initiators RA SLE Other Pt-yrs IR (95% CI) Pt-yrs IR (95% CI) Pt-yrs IR (95% CI) Any HCQ SE 12711 26 (23, 29) 1305 25 (18, 36) 567 41 (27, 61) Mono HCQ 3397 28 (24, 33) 797 28 (18, 42) 347 52 (32, 82) HCQ + csDMARDs 5473 28 (24, 33) 416 24 (13, 45) 127 32 (12, 84) HCQ + bDMARDs 3841 22 (17, 27) 93 11 (2, 77) 93 11 (2, 76) SE stopping HCQ 12711 13 (11, 15) 1305 12 (7, 19) 567 14 (6, 35) Mono HCQ 3397 12 (9, 16) 797 11 (6, 22) 347 14 (6, 35) HCQ + csDMARDs 5473 15 (12, 18) 416 13 (5, 31) 127 24 (8, 73) HCQ + bDMARDs 3841 12 (9, 16) 93 0 93 0 HCQ SE hospitalization 12711 0.31 (0.12, 0.84) 1305 0.77 (0.1, 5.4) 567 0 Any MTX SE 81234 51 (49, 52) 1516 59 (48, 72) 2145 72 (61, 84) Mono HCQ 22980 49 (46,52) 369 41 (25, 67) 802 62 (47, 82) MTX + csDMARDs 15447 72 (68, 77) 872 69 (53, 89) 229 131 (91, 187) MTX + bDMARDs 42748 43 (41, 45) 265 49 (29, 85) 1106 67 (53, 84) SE stopping MTX 91477 26 (25, 27) 1638 41 (32, 52) 2335 44 (36, 53) Mono MTX 26060 19 (17, 20) 390 33 (19, 57) 885 27 (17, 39) MTX + csDMARDs 17430 38 (36, 42) 933 48 (36, 65) 255 90 (60, 136) MTX + bDMARDs 47832 25 (23, 26) 305 26 (13, 53) 1188 47 (36, 61) MTX SE hospitalization 96436 2.4 (2.1, 2.8) 1674 5.4 (2.8, 10.3) 2502 3.2 (1.6, 6.4) By body system, the patterns of any SE were similar between HCQ or MTX initiators. Gastrointestinal SEs were the most common for both. Only ocular SEs were higher for HCQ vs. MTX. Multivariable Cox regression models of HCQ vs MTX SEs had a HR 0.46 (0.41 - 0.51) for RA, HR 0.47 [0.27 – 0.82] for SLE, and HR 0.51 [0.25 – 1.02] for other RMDs. While there was no difference in HCQ SEs by concomitant category or diagnoses, there was consistently higher SE rates in MTX for those on concomitant csDMARD vs monotherapy: RA HR 1.27 (1.16 - 1.38), SLE HR 1.97 (1.03 - 3.52), and other RMDs HR 2.04 (1.28 - 3.24). Conclusion This is the largest study yet to review patient-reported SEs from HCQ and MTX in RA and other RMDs over a 20-year period. While validating SEs was beyond the scope of the current study, we found an overall low incidence of SEs from HCQ use, with an adjusted rate half of those reported for MTX, and that this low rate did not differ by diagnosis or concomitant DMARD use. Disclosure of Interests None declared